The long range goal of this translational-engineering research project is to improve the vision of people who have abnormal corneal conditions such as keratoconus. In the previous grant period, we developed the ability to measure wavefront error in these eyes and we also developed customized soft corneal contact lenses that can compensate for their extreme higher-order ocular aberrations. Although these customized lenses can produce substantial improvements in visual performance, more needs to be done to restore acuity to normal values. In particular, the benefit was compromised by the unpredictable translation and rotation of the lens on the cornea, and may have been compromised by neural adaptation to the poor retinal image quality before correction. Our efforts during the next grant period are targeted at research that will overcome these limitations. Aim1.1 will stabilize the movement of customized soft contact lenses by sculpting the back surface profile to match the keratoconic anterior surface of cornea. Aim1.2 will optimize correction performance by selecting higher order aberrations to be corrected that have a significant impact on vision but are less sensitive to lens movements. Aim 1.3 will determine significance of the internal optics aberration in keratoconic eyes that cannot be corrected with conventional rigid gas permeable (RGP). Aim1.4 is to develop customized scleral lenses that sit stably on the sclera rather than cornea. Aim 1.5 is to compare the visual outcomes of these new, customized corneal and scleral contact lenses with conventional RGP lenses focusing on enhancing the benefits and reducing the limitations of the customized lenses. Aim 2 will test the hypothesis that patients with keratoconus may not be able to immediately achieve the full benefit of customized correction because of persisting neural adaptation to the poor retinal image quality before correction. Similar neural adaptation has been shown in normal eyes and in patients who have received laser refractive surgery, and we will test the extent of this adaptation in patients who have lived for years with extremely aberrated corneas. Such patients may require a long period of exposure to improved optical quality before reaping the full visual benefit of a customized optical correction. Therefore, we will also use a large-stroke adaptive optics system and customized scleral lenses for experiments on the effects of short- and long-term adaptation to higher order aberrations on perceived retinal image quality in these abnormal corneal patients. PUBLIC HEALTH RELEVANCE: The optical defects (higher order aberrations) induced by irregular shapes of the cornea with keratoconus cause significant degradation in visual quality as the disease advances. Customized contact lenses designed to correct the aberration of individual eyes can provide the patients with substantially improved visual performance.